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Updated: Jan 3, 2026
Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
PD-1 Signaling Promotes Control of Chronic Viral Infection by Restricting Type-I-Interferon-Mediated Tissue Damage
Saravanan Raju1, Daniel J Verbaro1, Takeshi Egawa1
1Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Abstract:
Immune responses are essential for pathogen elimination but also cause tissue damage, leading to disease or death. However, it is unclear how the host immune system balances control of infection and protection from the collateral tissue damage. Here, we show that PD-1-mediated restriction of immune responses is essential for durable control of chronic LCMV infection in mice. In contrast to responses in the chronic phase, PD-1 blockade in the subacute phase of infection paradoxically results in viral persistence. This effect is associated with damage to lymphoid architecture and subsequently decreases adaptive immune responses. Moreover, this tissue damage is type I interferon dependent, as sequential blockade of the interferon receptor and PD-1 pathways prevents immunopathology and enhances control of infection. We conclude that PD-1-mediated suppression is required as an immunoregulatory mechanism for sustained responses to chronic viral infection by antagonizing type-I interferon-dependent immunopathology.
Insights
Programmed cell death protein 1 (PD-1) restricts immune responses, crucial for controlling chronic viral infections and preventing tissue damage. Blocking PD-1 early paradoxically worsens viral persistence by increasing damaging inflammation.
Area of Science:
- Immunology
- Virology
- Pathology
Background:
- Immune responses eliminate pathogens but can cause self-tissue damage.
- The balance between infection control and preventing immunopathology is not fully understood.
Purpose of the Study:
- To investigate the role of PD-1 in balancing immune responses during chronic viral infections.
- To understand how PD-1 influences host defense and tissue integrity.
Main Methods:
- Used a mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection.
- Administered PD-1 blockade at different infection phases (subacute vs. chronic).
- Analyzed viral load, lymphoid architecture, immune cell function, and type I interferon signaling.
Main Results:
- PD-1 blockade in the subacute phase led to viral persistence and lymphoid tissue damage.
- This damage was dependent on type I interferon signaling.
- Sequential blockade of interferon receptor and PD-1 pathways restored immune control and reduced pathology.
Conclusions:
- PD-1-mediated immune suppression is essential for sustained control of chronic LCMV infection.
- PD-1 acts as an immunoregulatory mechanism to prevent type I interferon-driven immunopathology.
- Targeting PD-1 requires careful consideration of the infection phase to avoid detrimental effects.
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